OnTarget (February 12, 2007)
I. WHAT'S NEW?
Software Development at Target e*CRO™
II.
QUIZ - (Fill In The Blanks)
Aphrodisiacs & Health
III. HISTORY OF MEDICINE
Babylonian Medicine – Managed Care
IV. EPIDEMIOLOGY
Are You a Smart Vegetarian or Smart
Because You are a Vegetarian?
V. GENETICS
Horse Genome Sequenced - It's All About Twilight
VI. PEDIATRICS
New
Gene Identified in Patients With Osteogenesis Imperfecta
VII. ORTHOPEDICS
Proton Pump Inhibitors (PPIs)
and Risk of Hip Fracture
VIII. REGULATORY AFFAIRS
Types Of New Drug Applications - Section 505 of the Act
IX.
TARGET
HEALTH
I.
WHAT'S NEW
Software
Development at Target e*CRO™
We only sell software which we develop ourselves and
use in our drug and device development business. This is one of the ways we
assure quality and are different from other CROs. Our
Flagship Software products are Target e*CRF®, Target Document® and Target
Encoder™. For more information, please contact Dr.
Jules T. Mitchel.
Target Health is pleased to announce Target Document® is now ready for formal
release. Several of our clients have seen it, as well as several CROs. Target Document is 21 CRF Part 11 compliant and also
complies with ISO standards. Special introductory prices
available. We have a USER FRIENDLY interface and workflow.
Key features include:
- Web-based
- Works off a browser
- 21 CFR compliant
- eSignatures
- Unique access control to projects, folders
- One click user management
- Advanced administrative functions
- Many more
II. QUIZ (Fill In The Blanks)
Aphrodisiacs & Health
Aphrodisiacs are
based more on cultural myths than fact. Throughout history, certain foods,
beverages, drugs, and chemicals were hoped to have aphrodisiac powers. Named
after Aphrodite, the 1) ___ goddess of love, beauty, and fertility,
aphrodisiacs are substances that supposedly elicit desire, arousal, and enhance
drive and performance. The most famous reputed aphrodisiac of all is 2) ___
___, made from ground-up 3) ___, Lytta vesicatoria. Its active ingredient, cantharidin,
irritates the bladder and urethra, causing increased 4) ___ flow to the
genitals and sensations of warmth there. It may lead to abnormally prolonged or
constant 5) ___. Spanish Fly can be poisonous or even
fatal with prolonged use. Consider: moderate amounts of red wine, [with
antioxidant effects of raising 6) ___ and preventing blood clotting in vessels]
and 9 chocolate [antioxidant] kisses equaling 230 calories [sugar free, less
calories]. If the last two aphrodisiacs, lead to physical loving, the calories
burned, would be 150-200 calories per half hour, which in turn leads to a
deeper more rejuvenative 7) ___. HAPPY VALENTINE'S DAY!!!
ANSWERS: 1) Greek; 2) Spanish Fly; 3) beetles; 4) blood; 5) priapism; 6) HDL; 7) sleep
III. HISTORY
OF MEDICINE
Babylonian Medicine
– Managed Care
At the dawn of civilization, about 4,000 years ago, a massive pillar of stone
and written clay tablets already prescribed the concepts of managed care for
the practice of medicine. Codex Hammurabi established a sliding fee schedule
for services, promoted outcome measurements, which if not met, resulted in
harsh penalties, required medical records to document diseases and therapies,
included prescription benefits, fully explained patient's rights, and marketing
and advertising publicized the edicts of the King. Even though the managed care
was authoritarian, there were legal actions to insure justice and equity
particular to each social class in the kingdom. Tempered by time, the managed
care mandates of Codex Hammurabi can still be considered the genesis of the
current concepts of managed care. Edited by Alex
Hays.
IV. EPIDEMIOLOGY
Are You a Smart Vegetarian or
Smart Because You are a Vegetarian?
According to an
article published in the British Medical Journal (2007;334:245-248),
a study was performed to examine the relation between IQ in childhood and
vegetarianism in adulthood. The investigation was a prospective cohort study in
which IQ was assessed by tests of mental ability at age 10 years and
vegetarianism by self-report at age 30 years. Study participants included 8,170
men and women aged 30 years, who took part in the 1970 British cohort study, a
national birth cohort. The main outcome measures were self-reported
vegetarianism and type of diet followed. Results showed that 366 (4.5%) persons
said they were vegetarian, although 123 (33.6%) admitted eating fish or
chicken. Vegetarians were more likely to be female, to be of higher social
class (both in childhood and currently), and to have attained higher academic
or vocational qualifications. Interestingly, these socioeconomic advantages
were not reflected in their income. Higher IQ at age 10 years was associated
with an increased likelihood of being vegetarian at age 30 (odds ratio (OR) for
one standard deviation increase in childhood IQ score 1.38). IQ remained a
statistically significant predictor of being vegetarian as an adult after adjustment
for social class (both in childhood and currently), academic or vocational
qualifications, and gender (OR = 1.20). Exclusion of those who said they were
vegetarian but ate fish or chicken had little effect on the strength of this
association. According to the authors, higher scores for IQ in childhood are
associated with an increased likelihood of being a vegetarian as an adult.
V. GENETICS
Horse Genome Sequenced - It's
All About Twilight
The first draft
of the horse genome sequence has been deposited in public databases and is now
freely available for use. The $15 million effort to sequence the approximately
2.7 billion DNA base pairs in the genome of the horse (Equus caballus) was funded by the National Human Genome
Research Institute (NHGRI). Approximately 300,000 Bacterial Artificial
Chromosome (BAC) end sequences, which provide continuity when assembling a
large genome sequence, were contributed to the horse sequencing
project. Sequencing of the domestic horse genome began in 2006, building
upon a 10-year collaborative effort among an international group of scientists
to use genomics to address important health issues for equines, known as the Horse Genome Project. The
horse whose DNA was used in the sequencing effort is a Thoroughbred mare named Twilight from Cornell University in Ithaca, N.Y. Researchers obtained the DNA from a
small sample of the animal's blood. Twilight is stabled with a small
herd of horses that have been selected and bred for more than 25 years to study
the mechanisms that prevent maternal immunological recognition and destruction
of the developing fetus during mammalian pregnancy. The research has
implications in reproduction, clinical organ transplantation and immune
regulation. In addition to sequencing the horse genome, a map was produced of
horse genetic variation using DNA samples from a variety of modern and
ancestral breeds, including the Akel Teke, Andalusian, Arabian,
Icelandic, Quarter, Standardbred and Thoroughbred.
This map, comprised of 1 million signposts of variation called single
nucleotide polymorphisms, or SNPs, will provide a
genome-wide view of genetic variability in horses and help identify the
genetic contributions to physical and behavioral differences, as well as to
disease susceptibility. There are more than 80 known genetic conditions in
horses that are genetically similar to disorders seen in humans, including
musculoskeletal, neuromuscular, cardiovascular and respiratory diseases. The SNPs are available at the Broad Institute web
site and will be available shortly from NCBI's Single Nucleotide Polymorphism database. The initial sequencing assembly is
based on 6.8-fold coverage of the horse genome, which means, on average, each
base pair has been sequenced almost seven times over. Researchers can access
the horse genome sequence data through the following public databases: GenBank at NIH's National Center for Biotechnology
Information (NCBI); NCBI's Map Viewer; UCSC Genome Browser at
the University of California at Santa Cruz; and the Ensembl Genome Browser at the Wellcome Trust Sanger Institute in Cambridge, England.
VI. PEDIATRICS
New Gene Identified in
Patients With Osteogenesis Imperfecta
Osteogenesis imperfecta (OI) is a rare disorder that occurs in 1 out of 15,000 to 20,000 births.
Patients with OI have weaken bones, frequent fractures
and OI is sometimes fatal. The affected gene contains the information for a
protein designated P3H1 (prolyl 3-hydroxylase 1),
also known as leprecan. P3H1 is part of a complex of
proteins that is crucial for refining collagen to its final form. Collagen is
an important building block for bone. When the gene does not function, little
or no P3H1 is produced, resulting in defective collagen, and a form of OI.
About 85% of all OI cases are caused by mutations in the genes that contain the
information needed to make collagen. Some cases of OI, however, could not be
explained by mutations in the collagen gene. A new study, published online in
Nature Genetics (February 2007) has found a second genetic defect that accounts
for previously unexplained forms of OI. Although there is no treatment for the
disorder, the finding does allow OI experts to test families who have lost a
child to OI for the presence of the defective gene. Couples with a child affected
by this form of OI could be apprised of their risk for conceiving another child
with OI. Similarly, siblings of children affected by the defective gene can
also be counseled about their likelihood of carrying the gene.. The authors had earlier predicted that these unexplained OI cases might be
caused by absence of proteins that interact with, and chemically modify, type I
collagen. In a previous study (New England Journal of Medicine; December 28,
2006), a defect was discovered in the gene that codes for cartilage-associated
protein (CRTAP), one of the proteins that work with P3H1 during collagen
synthesis. Patients who have a loss of function of either CRTAP or P3H1 will
develop severe OI. Of the two genes, mutations in P3H1 are not always fatal, as
is the case when individuals do not have a functioning gene for CRTAP.
VII. ORTHOPEDICS
Proton Pump
Inhibitors (PPIs) and Risk of Hip Fracture
Proton pump inhibitors (PPIs) may interfere with calcium absorption through
induction of hypochlorhydria but they also may reduce
bone resorption through inhibition of osteoclastic vacuolar proton pumps. As a result, a study
published in the Journal of the American Medical Association (2006;296:2947-2953) was published to determine the association
between PPI therapy and risk of hip fracture. A nested case-control study was
conducted using the General Practice Research Database (1987-2003), which
contains information on patients in the
United Kingdom
. The study cohort
consisted of users of PPI therapy and nonusers of acid suppression drugs who
were older than 50 years. Cases included all patients with an incident hip
fracture. Controls were selected using incidence density sampling, matched for
gender, index date, year of birth, and both calendar period and duration of up-to-standard
follow-up before the index date. For comparison purposes, a similar nested
case-control analysis for histamine 2 receptor antagonists was performed. The
main outcome measure was the risk of hip
fractures associated with PPI use. During the study, there were 13,556 hip
fracture cases and 135,386 controls. The adjusted odds ratio (AOR) for hip
fracture associated with more than 1 year of PPI therapy was 1.44. The risk of
hip fracture was significantly increased among patients prescribed long-term
high-dose PPIs (AOR, 2.65; P<.001). The strength
of the association increased with increasing duration of PPI therapy (AOR for 1
year, 1.22; 2 years, 1.41; 3 years, 1.54; and 4 years, 1.59; P<.001 for all
comparisons). According to the authors, long-term PPI therapy, particularly at
high doses, is associated with an increased risk of hip fracture.
VIII. REGULATORY AFFAIRS
TARGET HEALTH excels in
Regulatory Affairs and works closely with many of its clients performing all
FDA submissions. TARGET HEALTH receives daily updates of new developments at
FDA. Each week, highlights of what is going on at FDA are shared to assure that
new information is expeditiously made available.
Types Of New Drug Applications - Section 505 of the Act
Section 505 of
the Food Drug and Cosmetic Act (the Act) describes three types of new drug
applications: (1) an application that contains full reports of investigations
of safety and effectiveness (section 505(b)(1)); (2) an application that
contains full reports of investigations of safety and effectiveness but where
at least some of the information required for approval comes from studies not
conducted by or for the applicant and for which the applicant has not obtained
a right of reference (section 505(b)(2)); and (3) an application that contains
information to show that the proposed product is identical in active
ingredient, dosage form, strength, route of administration, labeling, quality,
performance characteristics, and intended use, among other things, to a
previously approved product (section 505(j)). Section 505(b)(2)
was added to the Act by the Drug Price Competition and Patent Term Restoration
Act of 1984 (Hatch-Waxman Amendments). This provision expressly permits FDA to
rely, for approval of an NDA, on data not developed by the applicant. Sections
505(b)(2) and (j) together replaced FDA's paper NDA policy, which had permitted
an applicant to rely on studies published in the scientific literature to
demonstrate the safety and effectiveness of duplicates of certain post-1962
pioneer drug products (see 46 FR 27396, May 19, 1981). Enactment of the generic
drug approval provision of the Hatch-Waxman Amendments ended the need for
approvals of duplicate drugs through the paper NDA process by permitting approval
under 505(j) of duplicates of approved drugs (listed drugs) on the basis of
chemistry and bioequivalence data, without the need for evidence from
literature of effectiveness and safety. Section 505(b)(2)
permits approval of applications other than those for duplicate products and
permits reliance for such approvals on literature or on an Agency finding of
safety and/or effectiveness for an approved drug product.
For more information
about our expertise in Regulatory Affairs, please contact Dr. Jules T. Mitchel or Dr.
Glen Park.
IX. TARGET HEALTH
TARGET HEALTH INC. (www.targethealth.com) is a
full service e*CRO with full-time staff dedicated to all aspects of drug and
device development. Areas of expertise include Regulatory Affairs, comprising,
but not limited to, IND, IDE, NDA, PMA and 510(k) submissions, execution of
Clinical Trials, Project Management, Biostatistics and Data Management, Web
Trials, utilizing Target e*CRF®, our proprietary Internet-based Clinical Trial
System, and Medical Writing. TARGET HEALTH's Pharmaceutical Advisory Dream Team (PADT) assists companies in strategic
planning from Discovery to Market Launch. Let us help you on your next project.
TARGET HEALTH INC.
261 Madison Avenue
24th Floor
New York
,
NY
10016
Phone: (212) 681-2100; Fax (212) 681-2105
Target
Health Ad
www.targethealth.com
Dr. Jules T. Mitchel, President
Ms Joyce Hays, CEO
